A researcher is studying the Fas receptor (FasR), a protein widely expressed on cell surfaces. The signaling cascade of programmed cell death is initiated when FasR binds to its ligand (FasL), which is expressed on cytotoxic T cells. In an experiment, cancer cells that escaped elimination by the immune system were found to contain soluble Fas proteins that did not promote apoptosis. The soluble Fas proteins were shorter and lacked the transmembrane domain. DNA analysis of these cells revealed no FAS gene mutations. Which of the following is the most likely explanation for the formation of altered Fas proteins in these cancer cells?
Show Explanatory Sources
Alternative splicing is a process by which different combinations of DNA coding regions (exons) are selectively included or excluded from a mature messenger RNA (mRNA) transcript. This allows the DNA contained in a single gene to code for a functionally diverse group of proteins.
Splicing is a post-transcriptional modification that removes noncoding DNA regions (introns) from precursor-mRNA (pre-mRNA). The process is driven by a large protein complex (spliceosome) comprised of small nuclear ribonucleoproteins (snRNPs). Pre-mRNA splice sites are bound by the spliceosome, forming a lariat-shaped intermediate containing the introns. This intermediate is excised and the exons are joined, completing the splicing process.
Alternative splicing is a normal process that allows production of alternate sets of proteins in different tissues. It has also been implicated in various human diseases. Cancers in particular can use alternative splicing to evade innate defense mechanisms. The Fas receptor-Fas ligand interaction drives programmed cell death via the cytotoxic T-cell mediated extrinsic pathway. Cancer cells may develop the ability to splice out a particular exon that codes for the transmembrane domain of the Fas receptor (FasR), converting it to a soluble form that is not expressed on the cell surface, which allows the cells to evade apoptosis.
(Choice B) Polyadenylation is a post-transcriptional modification in which a tail comprised of multiple adenosine nucleotides is added to the 3' end of a new mRNA transcript. This process is necessary for the nuclear export and cytoplasmic stability of mRNA.
(Choice C) DNA methylation describes the process by which methyl groups are added to DNA, suppressing transcription of the methylated genes.
(Choice D) Polycistronic mRNA is often found in bacteria and contains multiple open reading frames that are translated into several proteins. In contrast, eukaryotic organisms have monocistronic mRNA, which codes for only one protein.
(Choice E) Ubiquitination is a process by which certain proteins are tagged with ubiquitin, a small regulatory protein, marking them for proteasomal degradation.
Educational objective:
Alternative splicing is a process by which a single gene can code for various unique proteins by selectively including or excluding different DNA coding regions (exons) into mature mRNA.